Several years ago we developed a rapid screening test for the erythrocyte enzyme (uro-porphyrinogen-I-synthetase, or URO synthetase) that is deficient in intermittent acute porphyria (IAP). We have exploited this test to initiate a screening study of a sample of individuals hospitalized for psychiatric illness at local State and Veterans Administration hospitals, and also an ambulatory population at a local prepaid health care facility. Of the 4,129 subjects screened in the psychiatric population, 11 could be classified by means of screening and quantitative URO synthetase assays, family history and urinary excretion of porphyrin precursors as having definite IAP. Another 9 subjects could be classified neither as normal nor as porphyric, and 9 subjects with positive screening tests were lost to follow-up. Of the 4,530 subjects screened at the prepaid ambulatory care facility, 20 individuals had positive screening tests. These individuals have not yet had the follow-up studies that are necessary to confirm or exclude the diagnosis of IAP. We propose in this protocol to continue our survey in these populations, to achieve an overall population size of more than 8,000 in the psychiatric subjects, and of about 18,000 in the ambulatory population. All subjects in either population who are ascertained to be suspect for IAP on the basis of the screening test will be studied further (quantitative erythrocyte URO synthetase; 24-hour urinary excretion of delta-aminolevulinic acid, porphobilinogen, family studies of URO synthetase, when possible) to confirm or exclude the diagnosis of IAP.